Preparation of halogenated alcohols

ABSTRACT

The invention provides an improved process for preparing halogenated alcohols of the formula CX1X2X3CH(OH)CH:C(CH3)2 (I, X1, X2, X3=halo) by reacting CX1X2X3H with 3-methylbut-2-en-1-al in the presence of a strong base and an inert solvent.

This a 371 application of PCT/GB95/02571 filed Nov. 2, 1995.

This invention relates to halogenated alcohols and more particularly toa process of preparing halogenated alcohols from haloalkanes.

The preparation of halogenated alcohols such as1,1,1-trichloro-4-methyl-3-penten-2-ol has previously been described (infor example J. Chem.Soc. (C), 1976,670). In this process a Grignardreagent such as isobutenylmagnesium chloride is reacted with chloral.However the Grignard reaction is essentially a laboratory procedure andis not inherently suitable for industrial production. An alternativeknown process involves the reaction of chloral with isobutylene underthe conditions of the Prins reaction but this can lead to a mixture ofthe desired product with the isomeric1,1,1-trichloro-4-methyl-4-pentene-2-ol and further treatment toisomerise this is required.

The present invention is concerned with an improved process which isapplicable to the preparation of the desired compounds and which issuitable for industrial manufacture.

Accordingly the present invention provides a process for preparing ahalogenated alcohol of formula:

    CX.sup.1 X.sup.2 X.sup.3 --CH(OH)CH═C(CH.sub.3).sub.2  (I)

wherein X¹, X² and X³ are halo, preferably chloro, bromo or fluoro,although not all of X¹, X² and X³ are necessarily the same, whichcomprises reacting a compound of formula:

    CX.sup.1 X.sup.2 X.sup.3 H                                 (II)

with 3-methylbut-2-en-1-al in the presence of a strong base and asolvent.

Compounds of formula (I) which may be made by the process include thosewherein X¹, X² and X³ are all chloro or all bromo. Particular examplesof such compounds of formula (I) include4-hydroxy-2-methyl-5,5,5-tribromopent-2-ene, and4-hydroxy-2-methyl-5,5,5-trichloropent-2-ene.

The compounds of formula (II) which are useful in the process of theinvention are halomethanes containing a single hydrogen atom, such aschloroform, and bromoform. 3-Methylbut-2-en-1-al is also known assenecialdehyde.

The process is conducted in the presence of a strong base, which isbelieved to act by generating a perhaloalkyl ion which then reacts withthe aldehyde. Suitable strong bases include alkali metal loweralkoxides, such as sodium or potassium alkoxides containing up to 6carbon atoms, for example sodium isopropoxide, potasium isopropoxide,sodium t-butoxide and potassium t-butoxide, but other bases such asalkali metal hydrides, for example sodium hydride, and amides, forexample sodamide, may also be used.

The process is preferably conducted at low temperatures to avoid theproduction of unwanted by-products. A preferred temperature is withinthe range -80° C. to 0° C., especially where a polar aprotic solvent isused. Particular examples of polar aprotic solvents which may be usefulin the process include amides such as dimethylformamide,dimethylacetamide, dibutylacetamide, cyclic ethers such astetrahydrofuran, tetrahydropyran and dioxan, glycol ethers such asethylene glycol dimethyl ether, and ethylene glycol diethyl ether, andsulphoxides such as dimethyl sulphoxide. However other inert solventssuch as aromatic hydrocarbons e.g. toluene may also be used.

The process is useful to produce the compounds of formula (I) in goodyield and purity and allows for easy isolation of the desired product.Any unreacted or excess compound of formula (II) can be readilyrecovered and recycled.

The compounds of formula (I) are useful as intermediates in a variety ofsynthetic procedures for the manufacture of useful products. Thus4-hydroxy-2-methyl-5,5,5-trichloropent-2-ene may be used in themanufacture of permethrin acid, a key intermediate for pyrethroidinsecticides, by the process set out in UK Patent No. 1528944.

The process of the invention is illustrated by the following Examples.

EXAMPLE 1

This Example illustrates the preparation of4-hydroxy-methyl-5,5,5-tribromopent-2-ene.

Sodium t-butoxide (1.2 ml of a 42% solution in dry dimethylformamide)was added dropwise over a period of 20 minutes to a stirred mixture ofbromoform (1.14 g), 3-methylbut-2-ene-1-al (0.32 g) and drytetrahydrofuran (15 ml) maintained at a temperature of -65° C. byexternal cooling under a nitrogen atmosphere, and the stirred mixturemaintained at that temperature for a further 30 minutes after completionof the addition. The external cooling was removed and the reactionquenched by dropwise addition of a saturated aqueous ammonium chloridesolution until the temperature had risen to -20° C. The mixture wasthereafter stirred until the temperature had risen to ambient (ca.20°C.).

The aqueous and organic phases were separated and the aqueous phaseextracted with dichloromethane (2×20 ml) and the extracts combined withthe organic phase and dried over anhydrous sodium sulphate. Afterremoval of the solvents by evaporation under reduced pressure theresidue was dissolved in hexane (20 ml) and the solution washed withbrine (3×5 ml) and dried over anhydrous sodium sulphate, andconcentrated by removal of the solvent under reduced pressure. Theresidue was dissolved in a mixture of ethyl acetate and petroleum ether(boiling range 40-60° C.) (1:6 parts by volume, 20 ml) and purified byloading onto a short silica column (3.75 cm) and eluting with the samemixture (400 ml). Successive fractions (3) were examined bychromatography to establish that the desired product was present in thefirst two fractions. The eluate was concentrated by evaporation of thesolvents under reduced pressure and the residue (1.14 g) identified bynuclear magnetic resovance spectroscopy and gas chromatographic-massspectral analysis as 4-hydroxy-2-methyl-5,5,5-tribromopent-2-ene.

EXAMPLE 2

This Example illustrates the preparation of4-hydroxy-2-methyl-5,5,5-trichloropent-2-ene.

The procedure and quantities used were similar to those of Example 1except that chloroform (0.54 g) was used in place of bromoform. Theproduct was obtained as a white crystalline solid (0.594 g).

We claim:
 1. A process for preparing a halogenated alcohol of formula:

    CX.sup.1 X.sup.2 X.sup.3 --CH(OH)CH═C(CH.sub.3).sub.2  (I)

wherein X¹, X² and X³ are halo, which comprises reacting a compound offormula:

    CX.sup.1 X.sup.2 X.sup.3 H                                 (II)

with 3-methylbut-2-en-1-al in the presence of an alkali metal alkoxide,at a temperature within the range -80 to 0° C. and an inert polaraprotic solvent.
 2. A process according to claim 1 wherein the alkalimetal alkoxide is selected from sodium isopropoxide, potassiumisopropoxide, sodium t-butoxide and potassium t-butoxide.
 3. A processaccording to claim 1 wherein the solvent is tetrahydrofuran.
 4. Aprocess as claimed in claim 1 wherein the compound of formula (II) isselected from chloroform and bromoform.
 5. A process as claim in claim 1wherein the temperature is below -20° C.
 6. A process for thepreparation of 4-hydroxy-2-methyl-5,5,5-trichloropent-2-ene whichcomprises reacting chloroform with 3-methylbut-2-en-1-al in the presenceof an alkali metal alkoxide, at a temperature within the range -80 to 0°C. and a polar aprotic solvent.
 7. A process as claimed in claim 6wherein the alkali metal alkoxide is sodium or potassium t-butoxide. 8.A process according to claim 6 wherein the temperature is below -20° C.9. A process according to claim 6 wherein the polar aprotic solvent istetrahydrofuran.